Pharmacokinetics, Safety and Immunogenicity of RPH-104 at a New Dosage and Different Doses Via Single Subcutaneous and Intravenous Administration in Healthy Volunteers
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT07206043
- Lead Sponsor
- R-Pharm International, LLC
- Brief Summary
The purpose of this study is to evaluate the safety, immunogenicity and pharmacokinetics of RPH-104 after single intravenous and subcutaneous administration to healthy volunteers at different doses
- Detailed Description
This clinical study is a single-center, simple-blind, randomized, comparative phase I clinical study conducted in 3 parallel cohorts:
In cohort A, a simple blind design is proposed with a single intravenous administration of the study drug at 3 increasing doses (N = 30, 10 volunteers per dose group): 80 mg, 160 mg, 320 mg
In cohort B, a simple blind design is proposed with a single subcutaneous administration of the study drug (80 mg/mL; 320 mg) compared to placebo (N = 20, 10 volunteers per drug and placebo group)
In cohort C, a simple blind design is proposed with a single subcutaneous administration of the study drug in two dosages (40 mg/mL and 80 mg/mL) in one dose (80 mg) to confirm the equivalence of these dosages (N = 80, 40 volunteers in each group)
The study will include the following periods:
1. Screening period: days -6 to -1 (before randomization and inclusion in the study)
2. Randomization: day 0
3. Main study period:days 1 to 50 (± 1)
The main period includes a single hospitalization of volunteers for at least 24 hours, as well as 9 outpatient visits in cohort A and 14 outpatient visits in cohorts B and C. It includes procedures related to the administration of the study drug, monitoring the study participant, and taking blood samples to measure the concentration of goflikicept, as well as a safety and immunogenicity panel
4. Safety monitoring period: days 51 - 61 (± 3). On day 61, a phone call will be made to collect information about safety
In order to monitor safety during the main sudy period, the following procedures will be carried out:
* In Cohort A, vital signs vital signs will be measured before drug administration and 15 min, 1 h, 2 h, 4 h, 12 h and 24 h after drug administration on days 3-50; physical examination will be performed on days 2, 6, 16, 30, 40, 50; electrocardiography (ECG) on days 3, 23, 50 day; assessment of hypersensitivity reactions to the drug in 2 h, 12 h, 24 h after the start of drug administration and on day 3; clinical blood test, biochemical blood test on 3, 6, 16, 23, 50 day; coagulogram on 3, 16, 50 day; general urinalysis on 6, 16, 23, 50 day.
* In Cohort B and C, vital signs vital signs will be measured before drug administration and in 2 h, 12 h and 24 h after drug administration on days 3-50; physical examination will be performed on days 2, 6, 16, 30, 40, 50; ECG on days 5, 23, 50 day; assessment of hypersensitivity reactions to the drug in 2 h, 12 h, 24 h after the start of drug administration and on day 3; clinical blood test, biochemical blood test on 5, 9, 16, 30, 50 day; coagulogram on 5, 16, 50 day; general urinalysis on 5, 16, 30, 50 day
* Women with preserved reproductive potential will additionally undergo blood analysis for hCG during screening, followed by a urine pregnancy test the day before the administration of RPH-104 (Day 0) and on Day 50
To assess the pharmacokinetics of RPH-104, volunteers will undergo periodic blood sampling (at a total of 18 points during the study for cohort A, and at 18 points for cohorts B and C)
* In cohort A, blood samples for the evaluation of RPH-104 pharmacokinetics will be taken before the infusion of RPH-104 on Day 1 (\< 60 min before infusion ) and in 30 min, 1 h (immediately after the end of the infusion), 1 h and 30 min, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, 72 h, 120 h, 192 h, 360 h, 528 h, 696 h, 936 h and 1176 h after the first administration of the drug (since the start of infusion)
* In cohort B and C, blood samples for the evaluation of RPH-104 pharmacokinetics will be taken before the infusion of RPH-104 on Day 1 (\< 60 min before infusion ) and in 4 h, 12 h, 24 h, 48 h, 72 h, 84 h, 96 h, 108 h, 144 h,120 h, 192 h, 264 h, 360 h, 528 h, 696 h, 936 h and 1176 h after the first administration of the drug (since the start of infusion)
To assess the immunogenicity of RPH-104, volunteers will undergo periodic blood sampling to determine the concentration of binding and neutralizing antibodies (at a total of 5 points in the study in all cohorts)
* In cohort A, blood sampling for immunogenicity testing is performed before the drug is administered (≤60 min before administration) and then in 360 h (day 16) (± 120 min), 696 h (day 30) (±24 h), 936 h (day 40) (±24 h), 1176 h (day 50) (±24 h) after administration of the drug. When binding antibodies are detected, their neutralizing activity (NAT) will additionally be determined
* In cohort B and C, blood sampling for immunogenicity testing is performed before the drug is administered (≤60 min before administration) and then in 360 h (day 16) (± 120 min), 696 h (day 30) (±24 h), 936 h (day 40) (±24 h), 1176 h (day 50) (±24 h) after administration of the drug. When binding antibodies are detected, their neutralizing activity (NAT) will additionally be determined
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 130
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: RPH-104, intravenous administration 80 mg RPH-104 80 mg Subjects received RPH-104 Intravenously once as a 60-minute infusion at a dosage of 40 mg/mL, at a dose of 80 mg. The volume of the infusion solution was 100 ± 8 mL Cohort A: RPH-104, intravenous administration 160 mg RPH-104 160 mg Subjects received RPH-104 Intravenously once as a 60-minute infusion at a dosage of 40 mg/mL, at a dose of 160 mg. The volume of the infusion solution was 100 ± 8 mL Cohort A: RPH-104, intravenous administration 320 mg RPH-104 320 mg Subjects received RPH-104 Intravenously once as a 60-minute infusion at a dosage of 40 mg/mL, at a dose of 320 mg. The volume of the infusion solution was 100 ± 8 mL Cohort B: RPH-104, subcutaneous administration 320 mg RPH-104 320 mg Subjects received a single subcutaneous injection of either RPH-104 at a dosage of 80 mg/mL, at a dose of 320 mg (2 injections of 2 mL), or a placebo (2 injections of 2 mL) Cohort B: Placebo Placebo Placebo Comparator, Placebo Cohort C: RPH-104, subcutaneous administration 80 mg (40 mg/mL) RPH-104 80 mg Subjects received a single subcutaneous injection of either RPH-104 at a dosage of 40 mg/mL, at a dose of 80 mg (1 injection of 2 mL) Cohort C: RPH-104, subcutaneous administration 80 mg (80 mg/mL) RPH-104 80 mg Subjects received a single subcutaneous injection RPH-104 at a dosage of 80 mg/mL, at a dose of 80 mg (1 injection of 1 mL)
- Primary Outcome Measures
Name Time Method The area under the plasma drug concentration-time curve (AUC) of RPH-104 from the moment of administration to infinity after a single injection of RPH-104 Up to day 61 ± 3 The area under the plasma drug concentration-time curve (AUC) of RPH-104 from the moment of administration to infinity after a single injection of RPH-104 (AUC(0-∞))
The maximum concentration of RPH-104 in the blood serum after a single injection of RPH-104 Up to day 61 ± 3 The maximum concentration of RPH-104 in the blood serum after a single injection of RPH-104 (Cmax).
Percentage of volunteers (%) with AEs and SAEs Up to day 61 ± 3 Percentage of volunteers (%) with AEs and SAEs
Percentage of volunteers (%) with AEs ≥ Grade 3 according to CTCAE 5.0 Up to day 61 ± 3 Percentage of volunteers (%) with AEs ≥ Grade 3 according to CTCAE 5.0
Percentage of volunteers (%) with ADRs and serious ADRs Up to day 61 ± 3 Percentage of volunteers (%) with ADRs and serious ADRs
Percentage of volunteers (%) with ADRs ≥ Grade 3 according to CTCAE 5.0 Up to day 61 ± 3 Percentage of volunteers (%) with ADRs ≥ Grade 3 according to CTCAE 5.0
Percentage of volunteers (%), who prematurely discontinued participation in the study due to AE/SAE and ADR/serious ADR Up to day 61 ± 3 Percentage of volunteers (%), who prematurely discontinued participation in the study due to AE/SAE and ADR/serious ADR
Percentage of volunteers (%) with AEs of special interest Up to day 61 ± 3 AEs of special interests include allergic and anaphylactic reactions, injection site reactions, infections, increased blood lipid levels, increased liver enzyme levels, drug-induced liver injury, neutropenia
Percentage of volunteers (%), who developed binding antibodies to RPH-104 Up to day 61 ± 3 Percentage of volunteers (%), who developed binding antibodies to RPH-104
Percentage of volunteers (%), who developed neutralizing antibodies to RPH-104 Up to day 61 ± 3 Percentage of volunteers (%), who developed neutralizing antibodies to RPH-104
- Secondary Outcome Measures
Name Time Method The area under the plasma drug concentration-time curve (AUC) of RPH-104 from the moment of administration to the last time point of sampling Up to day 50 ± 1 The area under the plasma drug concentration-time curve (AUC) of RPH-104 from the moment of administration to the last time point of sampling (AUC(0-1176))
The time to reach the maximum concentration of RPH-104 after a single injection Up to day 50 ± 1 The time to reach the maximum concentration of RPH-104 after a single injection (Tmax)
Apparent total clearance of RPH-104 after a single administration Up to day 50 ± 1 Apparent total clearance of RPH-104 after a single administration (Cl/F)
The half-life of RPH-104 after a single administration Up to day 50 ± 1 The half-life of RPH-104 after a single administration (T1/2)
The apparent volume of distribution of RPH-104 after a single administration Up to day 50 ± 1 The apparent volume of distribution of RPH-104 after a single administration (Vd/F)
The elimination constant of RPH-104 after a single administration Up to day 50 ± 1 The elimination constant of RPH-104 after a single administration (λz)
Trial Locations
- Locations (1)
Llc "Research Lab"
🇷🇺Moscow, Russia
Llc "Research Lab"🇷🇺Moscow, Russia